Endometrial Histology, Uterine Bleeding, and Metabolic Changes in Postmenopausal Women Using a Progesterone-Releasing Intrauterine Device and Oral Conjugated Estrogens for Hormone Replacement Therapy

Seven normal postmenopausal volunteers were enrolled in an 18-month study to evaluate a progesterone-releasing intrauterine device (P-IUD) used in conjunction with oral conjugated estrogen to control uterine bleeding and inhibit the endometrial effect of estrogen. Serum estradiol (E2) levels were elevated over baseline in all women throughout the course of the study. Serum progesterone (P4) did not change significantly after the insertion of the P-IUD. Endometrial thickness by ultrasound was <9.0 mm throughout the course of the study. Endometrial histology was interpreted as marked progesterone effect (decidualization) in all of the endometrial biopsies obtained at 6, 12, and 18 months. Uterine bleeding was infrequent after the third month after insertion of the P-IUD in all but one of the volunteers. Serum lipids obtained at 6 and 12 months showed an increase in triglycerides between these two intervals but no change in serum cholesterol. Two of the six volunteers had a decrease in HDL2 cholesterol, which is unexplained. Bone densitometry determinations of the lumbar spine and femoral neck showed an increase during the course of the study. The P-IUD was acceptable to the volunteers, and based on these data, appears effective in inhibiting the estrogen effect on the endometrium and reducing uterine bleeding. These attributes make targeting delivery of progesterone to the endometrium an attractive method for hormone replacement therapy.